No abstract

Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.

The activity of beta-carotene in patients with oral leukoplakia was confirmed. The responses produced were durable for 1 year.

No abstract

The objective was to evaluate the onset of action, analgesic efficacy and tolerability of Saridon*, a propyphenazone 150 mg/paracetamol 250 mg/caffeine 50 mg combination, in comparison with paracetamol 500 mg, aspirin 500 mg, ibuprofen 200 mg and placebo, by a pooled statistical analysis of eight studies. Out of 500 generally healthy patients (55.2% men, 44.8% women), average age 43.5 years, 329 (65.8%) had moderate and 171 (34.2%) severe acute dentoalveolar pain. More Saridon-treated patients reported 'pain gone/partly gone' and less 'pain unchanged or worse' compared with paracetamol, aspirin and placebo 30min (p = 0.009, p < 0.001, p = 0.001, respectively) and 60 min after dosing (p < 0.0001 for all). The difference with ibuprofen was observed 60 min after dosing (p < 0.01). Pain intensity differences 30 min and 60 min after dosing infer that Saridon has a faster onset of action than all of the other medications that it was compared with (ibuprofen at only 60 min after dosing). Total pain relief scores four hours after dosing were higher in the Saridon group compared with the paracetamol, ibuprofen, placebo (p < 0.0001 for all) and aspirin groups (p < 0.01). At the end of the study, patients assessed Saridon as more efficacious than the other study medications (p < 0.0001 for all). No serious adverse events were observed with any of the drugs studied. All medications were well tolerated. Twenty patients (4.0%) reported adverse events with no significant differences between groups. The most common adverse events were gastrointestinal disorders, followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac and general disorders. Saridon is an effective analgesic that combines the advantage of fast onset and effective analgesia as compared with paracetamol alone, ibuprofen, aspirin or placebo. The results of this pooled analysis of eight studies should be confirmed in a double-blind study, since seven of the studies included in this analysis were single blind.